A patient with Laron syndrome has short stature, low IGF-1 levels, and a normal or elevated growth hormone level. Genetic analysis reveals a mutation in the growth hormone receptor. Which signaling pathway is disrupted in this condition?

• A cAMP-PKA pathway
• B IP3-DAG pathway
• C JAK-STAT pathway ✓
• D MAP kinase pathway via RAS

Explanation

Growth hormone (GH) binds to its receptor, a type I cytokine receptor, which lacks intrinsic kinase activity. Ligand binding activates the associated JAK2 tyrosine kinase, which phosphorylates the receptor and recruits STAT transcription factors. STATs dimerize and translocate to the nucleus to regulate genes including IGF-1. Laron syndrome is GH receptor deficiency, so the JAK-STAT pathway is disrupted despite high GH levels.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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